Batool Mutar Mahdi1, Riyadh Mohamad Hasan2, Wafaa Hazim31 Department of Microbiology, HLA Typing Research Unit, Al-Kindy College of Medicine, University of Baghdad, Baghdad, Iraq2 Department of Surgery, Al-Kindy College of Medicine, University of Baghdad, Baghdad, Iraq3 Department of Microbiology, Al-Kindy College of Medicine, University of Baghdad, Baghdad, Iraq

Background: There are many risk factors associated with degree of development erosive esophagitis and its complications. Aim of the Study: To evaluate the effect of risk factors on severity of esophagitis and identify the most important risk factors among patients presenting to gastroscopy unit. Patients and Methods: Patients with upper gastrointestinal tract (GIT) symptoms were enrolled in gastroscope examination. For each participant, the body mass index (BMI), waist circumference, and immunoglobulin G Helicobacter pylori were done. Results: A total of 195 patients with upper GIT symptoms were examined by gastroscope. One hundred and twenty patients had erosive esophagitis (Grade II and III) (Group A): 75 of them were men (62.5%) and 45 (37.5%) were women. The rest 75 had gastroesophageal reflux disease Grade I (Group B), 52% of them were males, and the rest were females. Group A patients were more likely to be non-steroidal anti-inflammatory (NSAID) users (42.5%) than Group B (P = 0.0002). Group A was more likely to be obese (body mass index >30) (37.5%) (P = 0.015). Men have waist circumference >102 cm and women have a waist circumference >88 cm constitute 92.5% (P = 0.0001) of Group A. Patient with Group A who had hiatus hernia (HH) were (20%) (P = 0.0001) and those with H. pylori (35%) (P = 0.001). Conclusions: Obesity, abdominal obesity, NSAID, HH, and H. pylori infection are strong risk factors for gastroesophageal reflux grades.

Gastroesophageal reflux is a term used to describe the involuntary movement of gastric content into the esophagus associated with heartburn or regurgitation or with extraesophageal symptoms such as cough and sore throat.[1] These symptoms when occur twice weekly over several months are define as gastroesophageal reflux disease (GERD) as it is associated with erosive esophagitis, Barrett's esophagus (BE), and impairment patients' quality of life.[2] GERD physiopathology is complex and involves an interaction between many different environmental and the genetic factors among the various geographic regions.[3] Increased occurrence of GERD is associated with increased prevalence of obesity, an aging population, and a decreased prevalence of infection with Helicobacter pylori.[4] All causes could play a role in GERD occurrence, or they interact with the different GERD mechanisms. Epidemiological studies point to obesity as an important risk factor for GERD in adult's population.[5] This relationship exists not only for the symptoms occurrence but also for the complications of GERD like BE.[6] There is a conflicting study regarding obesity, it is postulated as a risk factor for GERD.[7] A number of studies demonstrate that an increased body mass index (BMI) of the human is associated with increased esophageal acid exposure and disrupts the barrier to gastroesophageal reflux mechanism.[8] In contrast, other studies have found no relationship between BMI and GERD.[9] Choi et al.[10] showed an association between obesity and GERD. The effects of BMI on GERD occurrence are independent on food type whether fruits, vegetables, dietary intake of fiber, or total caloric intake.[11] Weight gain assists GERD occurrence in the individuals,[12] and GERD symptoms may improve after decrease weight [13] and bariatric surgery such as Lap-Band system implantation.[14]

Therefore, we conducted this cross-sectional study to examine the association of BMI and other risk factors on grades of GERD.

Patients and Methods

It is an analytic cross-sectional study of consecutive 195 Iraqi Middle East individuals with upper gastrointestinal tract (GIT) symptoms, underwent gastroscopy in GIT center at Al-Kindy Teaching Hospital (Baghdad, Iraq) from January 2014 to July 2016. All patients referred to this unit were symptomatic. The inclusion criteria were suffering from the GERD symptoms (heartburn or acid regurgitation) for at least 3 times a week for a period of more than 3 months, chest pain, hoarseness, globus sensation (sensation of a lump, something sticking in the throat), and coughing. The exclusion criteria were patients who had a history of gastric surgery, peptic ulcer, gastric cancer, patients who had scleroderma or achalasia, esophageal varices, and patients who were on medications such as antacids, H2 blockers, proton pump inhibitors, and nonsteroidal anti-inflammatory drugs (NSAIDs) at the time of the study.

The study protocol was assessed and approved by the Scientific and Ethical Committee of Al-Kindy Medical College and Al-Kindy Teaching Hospital.

Esophagogastric examinations

All patients underwent upper gastrointestinal endoscopic examinations using gastroscope: GIF-H260; Olympus, Tokyo, Japan and Display screen; Olympus OEV-261H liquid crystal display monitor; Olympus, Tokyo, Japan. Endoscopic examinations which were performed by well-trained gastroenterologists with at least 5 years of endoscopy experience. The gastroesophageal junction was defined as the squamocolumnar junction and the proximal margin of gastric folds. The endoscopic findings were either Grade II (which is confluent erosive or exudative mucosal lesions that do not extend around the entire esophageal circumference) or Grade III (erosive or exudative mucosal lesions that cover the entire esophageal circumference and lead to inflammation of the wall without stricture) according to Los Angeles classification.[15] Histopathological study was done by taking specimens from gastric mucosa to confirm the diagnosis and presence of H. pylori. Hiatal hernia is part of the stomach squeezes upward into the thorax through an opining in the diaphragm with a circular extension of the gastric mucosa above the diaphragmatic hiatus. Other data were collected using questionnaire.

Serological tests

Blood samples were drawn from both groups into plain tube. Separated serums were analyzed for the presence cytotoxin-associated gene A antibodies immunoglobulin G (IgG) for H. pylori using an immunological test (immunochromatography test) and ELISA test (ACON, USA).

Evaluation of body mass index

BMI was calculated using a formula; body weight (kg) divided by the square of standing height (m). The BMI was grouped into three levels according to the WHO for the Western Pacific region:[16] normal weight - BMI <25 kg/m 2, overweight - BMI between 25 kg/m 2 and 30 kg/m 2, and obese - BMI >30 kg/m 2.[17]

Waist circumference

Place a tape measure around the body of the patients at the top of their hip bone, midway between the lowest rib and the iliac crest, and at the level of belly button. Make sure it's not tight and it's straight. The waist measured at the vertical level one inch above the navel. Ask the patient not to hold his breath while measuring. The risk of obesity-related disease is high if men have a waist circumference >102 cm and women have a waist circumference >88 cm.[16]

Statistical analysis

Frequencies of certain parameters were determined by direct counting and compared between two groups using Chi-square test using Minitab version 3.0 software. Data were expressed as mean ± standard deviation; P value <0.05 was considered statistically significant

Results

A total of 195 patients were enrolled in the gastroscope study. The results of the gastroscopy examination were 120 patients have GERD Grade II and III (Group A) and the rest 75 had GERD Grade I (Group B). Nearly 120 patients were Group A: 75 of them were males (62.5%) and 45 (37.5%) were females, and 45% of them their ages were between 40 and 59 years.

The rest of patients was 75 were Group B. Nearly 52% of them were males and the rest were females. About 48% of them, their ages were <40 years. Patients with Group A were more likely to be NSAID users (42.5%) than Group B (P = 0.0002). Patients who were obese (BMI >30) constituted 37.5% of Group A (P = 0.015). Patients with waist circumference >102 cm for males and 88 cm for females constitutes 92.5% of group A (P = 0.0001). Group A patients had more incidence of hiatus hernia (HH) (20%) (P = 0.011) and H. pylori infection (35%) (P = 0.001) as shown in [Table 1].

Seventy-eight patients out of Group A patients had GERD Grade II (65%). When comparing those patients with Group B (GERD I), they had a significant increase in NSAID consumption (50%) (P = 0.0001), 34.61% of them were overweight and obese with P value was 0.007, and 92.30% (P = 0.0001) of them had a waist circumference >102 cm in men and 88 cm in women. HH and H. pylori IgG antibodies constituted 15.38% (P = 0.021) and 26.92% (P = 0.0001), respectively, as demonstrated in [Table 2].

GERD patients (Grade III) constituted 35% of Group A patients. [Table 3] summarizes the comparison between this group of patients with Group B (Grade I). Nearly 50% of these patients, their ages were >60 years (P = 0.005) with BMI >30 (42.85%) (P = 0.015) and 92.85% of them had a waist circumference >102 cm in men and 88 cm in women (P = 0.0001). There is a significant increase in HH (28.57%) (P = 0.0001) and H. pylori + IgG (50%) (P = 0.0001).

In the present study, we evaluate 195 patients with upper GIT symptoms. One hundred and twenty of them had GERD (Grade II and III) by endoscopy. Obese patients (BMI >30) who have waist circumference >102 cm and women have a waist circumference >88 cm demonstrated a significant increase in risk of GERD (Grade II and Grade III) compared with Grade I (Group B), but overweight (BMI 25–30) patients only demonstrate increased risk of GERD (Grade II). Other variables such as HH and H. pylori showed increased association with GERD (Grade II and III) than in Grade I of GERD. These results were in accord with the previous studies that GERD was observed with obesity whereas GERD did not have a relation with overweight in comparison with normal BMI.[18],[19] Hampel et al.[20] meta-analysis also showed an association between obesity and GERD. Other study which is in agreement with our result that demonstrated an association between GERD and obesity.[21] There are many mechanisms by which obesity promotes GERD formation such as increased amount of fat in the abdomen leading in the increased the pressure in the stomach,[22] and increased relaxation of the sphincter.[23] In contrast, other studies reported no any relation with BMI and grades.[9] The reasons for this are the absence of real relation between them, selection of patients, procedures used in the work, and dissimilar study populations included in the study. Moreover, other works mentioned that association between them depends on symptoms of the patients and investigations used.

In this study, we found an association between grades of GERD with HH. This is in agreement with other studies that found increased weight leads to increased jeopardy for hernia, that end result in GERD.[24] Other study done by Stene-Larsen et al.[25] reported that 68% of patients with erosive esophagitis had concomitant hiatal hernia. Other works showed no relation between body mass and hernia [26] which both of them end in erosive esophagitis [27],[28],[29] due to destruction of junction between stomach and esophagus. In our study, we found a significant association between grades of GERD and HH. Old age with kyphosis increased frequency of HH and usage of drugs that affect the pressure of lower esophageal sphincter (LES) and movement.[30],[31] This study showed that obesity is more prone to increase the grade of GERD. This is because obesity may modify esophagogastric junction shape (EGJ), job, and destruction of this junction by promoting an axial partition between LES and the extrinsic crural diaphragm.[29] In addition to that increased waist circumference due to accumulation of fat as shown in our study. This is in agreement with other reports that found a higher mean visceral fat area is associated with erosive esophagitis due to accumulation of fat around the stomach generating external pressure.[32],[33] Hence, increased abdominal diameter measurement and BMI act as risk factors for BE.[6]

Other risk factor is H. pylori infection;[34] many studies have focused on the role of H. pylori in the development of GERD. Conflicting results exist concerning the influence of H. pylori on GERD symptoms and complications. This study showed a significant relation between H. pylori and grades of GERD. Meta-analysis study found that patients with GERD and H. pylori infection were 38.2% compared to 49.5% in non-GERD persons. Treatment of H. pylori did not affect the development of esophagitis.[35] Other meta-analysis studies observe a lack of GERD development after eradication of H. pylori in patients with dyspepsia.[36] These heterogeneous results of the studies due to selection and criteria of two groups, methods used in H. pylori diagnosis such as ELISA, histopathology, urease test, and criteria used for GERD diagnosis such as heartburn score, pH studies, and endoscopy. H. pylori affects D-cells in the gastric antrum that secretes somatostatin leads to high level of gastrin release and leads to increase acid secretion that leads to inflammation and cytokine secretions that alter parietal cell function. Consequently, H. pylori treatment in patients with duodenal ulcer and antral gastritis patients may get better GERD while GERD became worse in corpus gastritis.[37],[38] In addition to that, this contradictory may be due to strain of H. pylori and the ethnicity and genetic basis of the diseased group.[39] However, the patient's group was Iraqi Arab Asian population.

Other last factor is consumption of drugs such as NSAID; there is a significant increase in NSAID and grades of GERD development in our study. This is in agreement with other studies that showed NSAIDs are associated with GERD.[40],[41]

These medications may interfere with the EGJ function and reduce the protective mechanisms against acid.

Conclusions

Frequency of GERD is increasing worldwide. Its complex physiopathology depends on interactions genetic with environmental and lifestyle risk factors. Obesity and waist circumference both of them affect the integrity of the junction between stomach and esophagus and mechanisms of esophageal clearance promoting a special pressure gradient. HH and aging had an effect on GERD pathogenesis by affecting the function of LES and peristalsis. H. pylori and NSAID had an important effect on GERD.